Glucocorticoid receptor (GR) function is modulated by phosphorylation. As retinoic acid (RA) can activate some cytoplasmic kinases able to phosphorylate GR, we investigated whether RA could modulate GR phosphorylation in neuronal cells in a context of long-term glucocorticoid exposure. A 4-day treatment of dexamethasone (Dex) plus RA, showed that RA potentiated the (Dex)-induced phosphorylation on GR Serine 220 (pSer220GR) in the nucleus of a hippocampal HT22 cell line. This treatment increased the cytoplasmic ratio of p35/p25 proteins, which are major CDK5 cofactors. Roscovitine, a pharmacological CDK5 inhibitor, or a siRNA against CDK5 prevented RA potentiation of GR phosphorylation. Furthermore, roscovitine counter-acted the effect of RA on GR sensitive target proteins such as BDNF or tissue-transglutaminase. These data help understanding the interaction between RA- and glucocorticoid-signalling pathways, both of which have strong influences on the adult brain.

中文翻译：

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维甲酸通过细胞周期蛋白依赖性激酶5增加糖皮质激素受体的磷酸化。

糖皮质激素受体（GR）的功能通过磷酸化来调节。由于视黄酸（RA）可以激活一些能够磷酸化GR的胞质激酶，因此我们研究了在长期糖皮质激素暴露的情况下RA是否可以调节神经元细胞中GR的磷酸化。地塞米松（Dex）加RA的4天治疗表明，RA增强了海马HT22细胞系中GR丝氨酸220（pSer220GR）上（Dex）诱导的磷酸化。这种处理增加了p35 / p25蛋白的胞质比例，p35 / p25蛋白是主要的CDK5辅助因子。Roscovitine，一种药理性CDK5抑制剂或针对CDK5的siRNA可以防止RA增强GR磷酸化。此外，roscovitine抵消了RA对GR敏感的靶蛋白（如BDNF或组织转谷氨酰胺酶）的作用。